A drug delivery system (DDS) is intended to aid the delivery of medicine to a target site within the body to bring about a therapeutic effect. For example, if a medicine is excreted too fast from the body due to its low absorption or bioavailability rates, a DDS may be used to modify the drug release profile. Medicines with serious adverse effects need to be delivered to target tissues or cells only. Many currently available anticancer agents, for example, exhibit cytotoxicity on normal cells as well as on cancerous cells. The substantial delivery of anticancer agents to cancerous cells or tissues would reduce the agony and inconvenience of cancer patients during treatment.
Since the first use thereof in the 1960s, liposomes have been widely studied for their use in DDS. Advances in liposome research have constructed, in conjugation with polymers such as polyethylene glycol (PEG) studding the outside of the membrane, so-called stealth liposomes, which can avoid detection by the body's immune system. The PEG coating allows for longer circulatory half-life for the drug delivery mechanism. In practice, DOXIL, a pegylated liposome-encapsulated form of doxorubicin, has been developed. However, liposomes and stealth liposomes themselves cannot deliver drugs to target cells or tissues because they lack the ability to recognize the target cells or tissues. To allow liposomes to bind to a specific target, studies have recently been directed toward the impartment of targeting ligands, such as monoclonal antibodies, to liposomes, but none of them have yet passed clinical tests and been successfully commercialized.
Instead of artificially synthesized liposomes consisting of lipids, naturally occurring cellular membranes are used to develop delivery systems. Vesicles derived from transformed microorganisms grown in drug-containing media are used for drug delivery [WO 2005/079854, “Compositions and methods for targeted in vitro and in vivo drug delivery to mammalian cells via bacterially derived intact minicells”]. When vesicles, usually comprised of bacterial cell membranes, are derived from Gram-negative bacteria, they have lipopolysaccharides that may cause various adverse effects including immune responses within the body. In addition, a delivery system utilizing a human red blood cell membrane is disclosed [US 2007/0243137, “Cell and sub-cell methods for imaging and therapy”]. Materials, if loaded into vesicles constructed with red blood cell membranes, can be maintained for a long period of time in the blood because red blood cells last for 120 days in the blood. The loaded materials include image contrasting agents for enhancing medical imaging, and metal particles or ions for radiotherapy. However, the red blood cell-derived vesicles cannot be used to deliver drugs to specific cells or tissues because red blood cells lack an ability to recognize specific cells or tissues. Further, red blood cells are anucleated, therefore, transformation for the expression of ligands recognizing specific cells or tissues on the surface of red blood cell is not possible.